- Despite Cartoon Network Studios having involvement in the film, Warner Bros. Pictures didn’t distribute it.
- The fourth Cartoon Network theatrical film, the first being The Powerpuff Girls Movie, the second being Regular Show: The Movie, and the third being The Grim Adventures of Billy & Mandy.
- Unlike the first film, The Powerpuff Girls Movie Part II succeeded at the box office.
- Sony Pictures Animation's first fully 2D animated movie.
- Sony Pictures Animation's third film with an August release after The Angry Birds Movie 2 and Hotel Transylvania 4.
- The second Cartoon Network film to be distributed outside of Warner Bros. Pictures.
- This marks the first time since Eight Crazy Nights, where Columbia Pictures released a fully 2D animated theatrical film.
- The first Powerpuff Girls movie to use flash-animation rather than its traditional animation from the first film.
- Sony Pictures Animation's first film in collaboration with Cartoon Network.
- Unlike the first film, which was produced in 1.85:1, The Powerpuff Girls Movie Part II was produced in a 2.35:1 aspect ratio.
- The second Cartoon Network film to be produced in 2.35:1.
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